PD-1 immune checkpoint blockade reduces pathology and improves memory in mouse models of Alzheimer's disease
PD-1 immune checkpoint blockade reduces pathology and improves memory in mouse models of Alzheimer's disease
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DOI：
10.1038/nm.4022
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发表时间：
2016-02-01
期刊：
影响因子：
82.9
通讯作者：
Schwartz, Michal
中科院分区：
文献类型：
--
作者：
Baruch, Kuti;Deczkowska, Aleksandra;Schwartz, Michal
系统性免疫抑制可能会削弱大脑修复所需的保护性细胞介导的免疫反应的能力。通过使用阿尔茨海默病（AD）的小鼠模型，我们表明针对程序性死亡-1（PD-1）途径的免疫检查点阻断引起干扰素（IFN）-γ依赖性全身免疫应答，随后是单核细胞衍生的巨噬细胞向大脑的募集。当在具有确定病理学的小鼠中诱导时，这种免疫应答导致大脑淀粉样蛋白β（A β）斑块的清除和认知性能的改善。需要重复治疗以维持对疾病病理学的长期有益作用。这些发现表明，免疫检查点可能是治疗AD的靶点。
Systemic immune suppression may curtail the ability to mount the protective, cell-mediated immune responses that are needed for brain repair. By using mouse models of Alzheimer's disease (AD), we show that immune checkpoint blockade directed against the programmed death-1 (PD-1) pathway evokes an interferon (IFN)-gamma-dependent systemic immune response, which is followed by the recruitment of monocyte-derived macrophages to the brain. When induced in mice with established pathology, this immunological response leads to clearance of cerebral amyloid-beta (A beta) plaques and improved cognitive performance. Repeated treatment sessions were required to maintain a long-lasting beneficial effect on disease pathology. These findings suggest that immune checkpoints may be targeted therapeutically in AD.